Utility of MRI for cervical spine clearance after blunt traumatic injury: a meta-analysis.

OBJECTIVES: To quantify the rate of unstable injuries detected by MRI missed on CT in blunt cervical spine (CS) trauma patients and assess the utility of MRI in CS clearance. METHODS: We undertook a systematic review of worldwide evidence across five major medical databases and performed a meta-analysis. Studies were included if they reported the number of unstable injuries or gave enough details for inference. Variables assessed included severity, CT/MRI specifications, imaging timing, and outcome/follow-up. Pooled incidences of unstable injury on follow-up weighted by inverse-of-variance among all included and obtunded or alert patients were reported. RESULTS: Of 428 unique citations, 23 proved eligible, with 5,286 patients found, and 16 unstable injuries reported in five studies. The overall pooled incidence is 0.0029 %. Among studies reporting only obtunded patients, the pooled incidence is 0.017 %. In alert patients, the incidence is 0.011 %. All reported positive findings were critically reviewed, and only 11 could be considered truly unstable. CONCLUSIONS: There is significant heterogeneity in the literature regarding the use of imaging after a negative CT. The finding rate on MRI for unstable injury is extremely low in obtunded and alert patients. Although MRI is frequently performed, its utility and cost-effectiveness needs further study. KEY POINTS: • There were 16 unstable injuries on follow-up MRI among 5286 patients. • The positive finding rate among obtunded patients was 0.12 %. • The positive finding rate among alert, awake patients was 0.72 %. • MRI has a high false-positive rate; its utility mandates further studies. • The use and role of "confirmatory" tests shows wide variations.

Cost-effectiveness of lumbar discectomy and single-level fusion for spondylolisthesis: experience with the NeuroPoint-SD registry.

OBJECT: There is significant practice variation and uncertainty as to the value of surgical treatments for lumbar spine disorders. The authors' aim was to establish a multicenter registry to assess the efficacy and costs of common lumbar spinal procedures by using prospectively collected outcomes. METHODS: An observational prospective cohort study was completed at 13 academic and community sites. Patients undergoing single-level fusion for spondylolisthesis or single-level lumbar discectomy were included. The 36-Item Short Form Health Survey (SF-36) and Oswestry Disability Index (ODI) data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Power analysis estimated a sample size of 160 patients: lumbar disc (125 patients) and lumbar listhesis (35 patients). The quality-adjusted life year (QALY) data were calculated using 6-dimension utility index scores. Direct costs and complication costs were estimated using Medicare reimbursement values from 2011, and indirect costs were estimated using the human capital approach with the 2011 US national wage index. Total costs equaled $14,980 for lumbar discectomy and $43,852 for surgery for lumbar spondylolisthesis. RESULTS: There were 198 patients enrolled over 1 year. The mean age was 46 years (49% female) for lumbar discectomy (n = 148) and 58.1 years (60% female) for lumbar spondylolisthesis (n = 50). Ten patients with disc herniation (6.8%) and 1 with listhesis (2%) required repeat operation at 1 year. The overall 1-year follow-up rate was 88%. At 30 days, both lumbar discectomy and single-level fusion procedures were associated with significant improvements in ODI, visual analog scale, and SF-36 scores (p = 0.0002), which persisted at the 1-year evaluation (p < 0.0001). By 1 year, more than 80% of patients in each cohort who were working preoperatively had returned to work. Lumbar discectomy was associated with a gain of 0.225 QALYs over the 1-year study period ($66,578/QALY gained). Lumbar spinal fusion for Grade I listhesis was associated with a gain of 0.195 QALYs over the 1-year study period ($224,420/QALY gained). CONCLUSIONS: This national spine registry demonstrated successful collection of high-quality outcomes data for spinal procedures in actual practice. These data are useful for demonstrating return to work and cost-effectiveness following surgical treatment of single-level lumbar disc herniation or spondylolisthesis. One-year cost per QALY was obtained, and this cost per QALY is expected to improve further by 2 years. This work sets the stage for real-world analysis of the value of health interventions.

System-wide integration of patient reported outcome measure collection through an electronic medical record system: A state-wide retrospective study.

BACKGROUND AND PURPOSE: In spine neurosurgery practice, patient-reported outcome measures (PROMs) are tools used to convey information about a patient's health experience and are an integral component of a clinician's decision-making process as they help guide treatment strategies to improve outcomes and minimize pain. Currently, there is limited research showing effective integration strategies of PROMs into electronic medical records. This study aims to provide a framework for other healthcare systems by outlining the process from start to finish in seven Hartford Healthcare Neurosurgery outpatient spine clinics throughout the state of Connecticut. METHODS: On March 1, 2021, a pilot implementation program began in one clinic and on July 1, 2021, all outpatient clinics were implementing the revised clinical workflow that included the electronic collection of PROMs within the electronic health record (EHR). A retrospective chart analysis studied all adult (18+) new patient visits in seven outpatient clinics by comparing the rates of PROMs collection in Half 1 (March 1, 2021-August 31, 2022) and in Half 2 (September 1, 2022-February 28, 2022) across all sites. Additionally, patient characteristics were studied to identify any variables that may lead to higher rates of collection. RESULTS: During the study period, 3528 new patient visits were analyzed. There was a significant change in rates of PROMs collection across all departments between H1 and H2 (p < 0.05). Additional significant predictors for PROMs collection were the sex and ethnicity of the patient as well as the provider type for the visit (p < 0.05). CONCLUSIONS: This study proved that implementing the electronic collection of PROMs into an already existing clinical workflow reduces previously identified collection barriers and enables PROMs collection rates that meet or exceed current benchmarks. Our results provide a successful step-by-step framework for other spine neurosurgery clinics to implement a similar approach.

Decompressive hemicraniectomy in a 19-month-old female after malignant cerebral infarction.

Malignant cerebral infarction is a life-threatening condition with case fatality rates of approximately 80% in adults with malignant infarction of the middle cerebral artery. No medical treatment has been proven effective for this condition. Decompressive hemicraniectomy within 48 h of massive cerebral infarction significantly reduces mortality and improves outcome in adults 18-60 years of age. However, there is very limited data available about the role of decompressive hemicraniectomy in children with acute malignant cerebral infarction. We present the case of a 19-month-old female who presented with progressive encephalopathy and right hemiparesis. Computed tomography and magnetic resonance imaging of the brain showed massive cerebral infarction in the distribution of the left carotid artery with midline shift and impeding brain stem herniation. She underwent emergent decompressive hemicraniectomy with duraplasty and placement of an intracranial pressure monitor. Intracranial pressure was controlled with sedation and the patient was extubated on postoperative day 4. Extensive stroke workup was negative. Cranioplasty was performed at 3 months post-op. At the 6-month follow-up, she had an excellent recovery (modified Rankin scale of 1). Decompressive hemicraniectomy should be considered for the treatment of cerebral edema in children with malignant cerebral infarction. This may improve mortality and functional outcome compared to medical therapy alone. Due to the rare occurrence of stroke in children, more reports of decompressive hemicraniectomy are encouraged.

Cervical Cord-Canal Mismatch: A New Method for Identifying Predisposition to Spinal Cord Injury.

The risk for spinal cord injuries (SCIs) ranging from devastating traumatic injuries, compression because of degenerative pathology, and neurapraxia is increased in patients with congenital spinal stenosis. Classical diagnostic criteria include an absolute anteroposterior diameter of <12-13 mm or a Torg-Pavlov ratio of <0.80-0.82; however, these factors do not take into account the size of the spinal cord, which varies across patients, independent of canal size. Recent large magnetic resonance imaging studies of population cohorts have allowed newer methods to emerge that account for both cord and canal size by measuring a spinal cord occupation ratio (SCOR). A SCOR defined as ≥70% on midsagittal imaging or ≥80% on axial imaging appears to be an effective method of identifying cord-canal mismatch, but requires further validation. Cord-canal size mismatch predisposes patients to SCI because of 1) less space within the canal lowering the amount of degenerative changes needed for cord compression, and 2) less cerebrospinal fluid surrounding the spinal cord decreasing the ability to absorb kinetic forces directed at the spine. Patients with cord-canal mismatch have been reported to be at a substantially higher risk of traumatic SCI, and present with degenerative cervical myelopathy at a younger age than patients without cord-canal mismatch. However, neurologic outcome after SCI has occurred does not appear to be different in patients with or without a cord-canal mismatch. Recognition that canal and cord size are both factors which predispose to SCI supports that cord-canal size mismatch rather than a narrow cervical canal in isolation should be viewed as the underlying mechanism predisposing to SCI.

Management of acute traumatic spinal cord injury.

OPINION STATEMENT: Spinal cord injury (SCI) causes significant morbidity and mortality. Clinical management in the acute setting needs to occur in the intensive care unit in order to identify, prevent, and treat secondary insults from local ischemia, hypotension, hypoxia, and inflammation. Maintenance of adequate perfusion and oxygenation is quintessential and a mean arterial pressure >85-90 mm Hg should be kept for at least 1 week. A cervical collar and full spinal precautions (log-roll, flat, holding C-spine) should be maintained until the spinal column has been fully evaluated by a spine surgeon. In patients with SCI, there is a high incidence of other bodily injuries, and there should be a low threshold to assess for visceral, pelvic, and long bone injuries. Computed tomography of the spine is superior to plain films, as the former rarely misses fractures, though caution needs to be exerted as occipitocervical dislocation can still be missed. To reliably assess the spinal neural elements, soft tissues, and ligamentous structures, magnetic resonance imaging is indicated and should be obtained within 48-72 h from the time of injury. All patients should be graded daily using the American Spinal Injury Association classification, with the first prognostic score at 72 h postinjury. Patients with high cervical cord (C4 or higher) injury should be intubated immediately, and those with lower cord injuries should be evaluated on a case-by-case basis. However, in the acute setting, respiratory mechanics will be disrupted with any spinal cord lesion above T11. Steroids have become extremely controversial, and the professional societies for neurosurgery in the United States have given a level 1 statement against their use in all patients. We, therefore, do not advocate for them at this time. With every SCI, a spine surgeon must be consulted to discuss operative vs nonoperative management strategies. Indications for surgery include a partial or progressive neurologic deficit, instability of the spine not allowing for mobilization, correction of a deformity, and prevention of potential neurologic compromise. Measures to prevent pulmonary emboli from deep venous thromboembolisms are necessary: IVC filters are recommended in bedbound patients and low-molecular weight heparins are superior to unfractionated heparin. Robust prevention of pressure ulcers as well as nutritional support should be a mainstay of treatment. Lastly, it is important to note that neurologic recovery is a several-year process. The most recovery occurs in the first year following injury, and therefore aggressive rehabilitation is crucial.

Imaging of lumbar spinal surgery complications.

UNLABELLED: Lumbar spine surgery for spinal stenosis is a frequently performed procedure and was the fastest growing type of surgery in the US from 1980 to 2000. With increasing surgical invasiveness, postoperative complications also tend to be higher. Cross-sectional imaging techniques (CT and MRI) are more sensitive than radiographs and play an increasingly important role in evaluation of patients with lumbar spine surgery. Their use in patients with metallic implants is somewhat limited by artefacts, which can obscure pathology and decrease accuracy and reader confidence. Metal artefact reduction techniques have been developed, which can significantly improve image quality and enable early detection of postoperative complications. Complications can occur throughout postoperative course. Early complications include hardware displacement, incidental durotomy, postoperative collections-most commonly seroma, and less likely haematoma and/or infection. Incidental durotomy with CSF leak causing intracranial hypotension has characteristic MR brain findings and diagnosis of occult leak sites have been improved with use of dynamic CT myelography. Haematomas, even when compressing the thecal sac, are usually asymptomatic. Early infection, with nonspecific MR findings, can be diagnosed accurately using dual radiotracer studies. Delayed complications include loosening, hardware failure, symptomatic new or recurrent disc herniation, peri-/epidural fibrosis, arachnoiditis, and radiculitis. TEACHING POINTS: • CT and MRI play an increasingly important role in evaluation of patients with lumbar spine surgery • Complications can occur throughout the postoperative course and early detection is critical • Artefact reduction techniques can improve image quality for early and improved detection of complications.

Predictors of Vertebral Artery Injury in Isolated C2 Fractures Based on Fracture Morphology Using CT Angiography.

STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To determine C2 fracture patterns associated with vertebral artery injury (VAI) as assessed by computed tomography angiography. SUMMARY OF BACKGROUND DATA: The incidence of C2 fracture hospitalizations has increased significantly in the last decade. The vertebral arteries are susceptible to injury as each courses through the C2 transverse foramen. Early screening for VAI to institute antithrombotic treatment is critical to prevent ischemic neurological sequelae. Imaging-based fracture classification schemes to determine which patterns are predictors of VAI in isolated C2 fractures using computed tomography angiography have not been described. METHODS: Cervical spine computed tomographic (CT) scans at a level I trauma center were reviewed for isolated C2 fractures from 2004 to 2014 under institutional board review approval. Exclusion criteria included penetrating injury or additional cervical/occipital fractures. Fractures were classified using multiplanar CT scans into type I/II/IIa/III spondylolisthesis, type I/IIA/IIB/IIC/III dens, transverse foramen (displacement/comminution/intraforaminal fragments), and miscellaneous vertebral body fractures. Corresponding CT angiograms were assessed for VAI on the basis of the Denver grading criteria. Fisher exact test and Student t test were performed to determine predictors of VAI on the basis of fracture type. RESULTS: Sixty-seven patients met inclusion criteria. Fracture pattern analysis revealed that the majority were dens fractures (50.8%) and traumatic spondylolisthesis (41.8%); 29.9% had miscellaneous coronal/sagittal fractures and 22.4% were a combination.VAI was identified in 37.3% of patients with isolated C2 fractures, and 88% of patients had transverse foramen involvement. Fracture patterns significantly associated with VAI were type III dens and transverse foramen fractures with intraforaminal fragments, with or without comminution. CONCLUSION: The C2 fracture pattern most associated with VAI was comminuted transverse foramen fracture with intraforaminal fragments. Transverse foramen fracture alone was not found to be significant. These results help stratify patients with isolated C2 fractures who are at high VAI risk and should be further evaluated with computed tomography angiography. LEVEL OF EVIDENCE: 3.

The Neuroprotective Effect of Syringic Acid on Spinal Cord Ischemia/Reperfusion Injury in Rats.

Acute arterial occlusions via different vascular pathologies are the main causes of spinal cord ischemia. We investigated neuroprotective effects of syringic acid on spinal cord ischemia injury in rats. Rats were divided into four groups: (I) sham-operated control rats, (II) spinal cord ischemia group, (III) spinal cord ischemia group performed syringic acid, and (IV) spinal cord ischemia group performed methylprednisolone intraperitoneally. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. A significant decrease was seen in malondialdehyde levels in group III as compared to group II (P < 0.05). Besides these, nuclear respiratory factor-1 and superoxide dismutase activity of group III were significantly higher than group II (P < 0.05). In histopathological samples, when group III was compared with group II, there was a significant decrease in numbers of apoptotic neurons (P < 0.05). In immunohistochemical staining, BECN1 and caspase-3-immunopositive neurons were significantly decreased in group III compared with group II (P < 0.05). The neurological deficit scores of group III were significantly higher than group II at twenty-fourth hour of ischemia (P < 0.05). Our study revealed that syringic acid pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required for syringic acid to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

Intracerebral hematoma from aneurysm rupture.

OBJECT: Patients who present with an intraparenchymal hematoma associated with a ruptured aneurysm usually require urgent clot evacuation and aneurysm obliteration. The impact of the presence of hematoma on outcome has been poorly characterized. The authors report on 460 patients who had dense subarachnoid hemorrhage (SAH) (Fisher Grades 3 and 4) with and without associated hematoma. METHODS: Of the 959 consecutive patients who presented with SAH, 460 patients with Fisher Grade 3 and 4 SAH were analyzed and divided into two groups: those with (Group 1) and those without (Group 2) hematoma. The presenting Hunt and Hess grade and 6-month outcomes of the two groups were compared. Of the 460 patients, 116 (25%) had intraparenchymal hematomas and admission Hunt and Hess grades were worse in Group 1 compared with Group 2. Outcome scores were worse for Group 1 compared with Group 2; however, when comparing Group 1 and Group 2 within the same initial Hunt and Hess score, there was no statistical difference in outcome. CONCLUSIONS: Intraparenchymal hematoma in association with SAH does not differ significantly from those patients without associated hematomas. We therefore recommend aggressive clot evacuation and aneurysm obliteration.

The efficacy of lumbar discectomy and single-level fusion for spondylolisthesis: results from the NeuroPoint-SD registry: clinical article.

OBJECT: There is significant practice variation and considerable uncertainty among payers and other major stakeholders as to whether many surgical treatments are effective in actual US spine practice. The aim of this study was to establish a multicenter cooperative research group and demonstrate the feasibility of developing a registry to assess the efficacy of common lumbar spinal procedures using prospectively collected patient-reported outcome measures. METHODS: An observational prospective cohort study was conducted at 13 US academic and community sites. Unselected patients undergoing lumbar discectomy or single-level fusion for spondylolisthesis were included. Patients completed the 36-item Short-Form Survey Instrument (SF-36), Oswestry Disability Index (ODI), and visual analog scale (VAS) questionnaires preoperatively and at 1, 3, 6, and 12 months postoperatively. Power analysis estimated a sample size of 160 patients: 125 patients with lumbar disc herniation, and 35 with lumbar spondylolisthesis. All patient data were entered into a secure Internet-based data management platform. RESULTS: Of 249 patients screened, there were 198 enrolled over 1 year. The median age of the patients was 45.0 years (49% female) for lumbar discectomy (n = 148), and 58.0 years (58% female) for lumbar spondylolisthesis (n = 50). At 30 days, 12 complications (6.1% of study population) were identified. Ten patients (6.8%) with disc herniation and 1 (2%) with spondylolisthesis required reoperation. The overall follow-up rate for the collection of patient-reported outcome data over 1 year was 88.3%. At 30 days, both lumbar discectomy and single-level fusion procedures were associated with significant improvements in ODI, VAS, and SF-36 scores (p ≤ 0.0002), which persisted over the 1-year follow-up period (p < 0.0001). By the 1-year follow-up evaluation, more than 80% of patients in each cohort who were working preoperatively had returned to work. CONCLUSIONS: It is feasible to build a national spine registry for the collection of high-quality prospective data to demonstrate the effectiveness of spinal procedures in actual practice. Clinical trial registration no.: 01220921 (ClinicalTrials.gov).

Two-level thoracic pedicle subtraction osteotomy for progressive post-laminectomy kyphotic deformity following resection of an unusual thoracolumbar intradural extramedullary tumor.

The authors report a case in which multilevel thoracic pedicle subtraction osteotomy (PSO) was performed to correct post-laminectomy kyphotic deformity in a 9-year-old boy presenting with worsening lower-extremity neurological deficits. Five years prior to presentation, the patient underwent multilevel thoracolumbar laminectomies for resection of an atypical teratoid/rhabdoid tumor (AT/RT), a rare lesion that typically occurs intracranially and has a poor prognosis, making this particular presentation unusual and the patient's subsequent postoperative course remarkable. No fusion was undertaken at the time of resection, given the patient's age and presumptive poor prognosis. Over the next 5 years, the patient developed progressive thoracolumbar kyphotic deformity, with a Cobb angle greater than 110°, despite bracing, and bilateral lower-extremity weakness requiring ankle-foot orthotics for continued ambulation due to progressive foot drop. Worsening gait and the onset of respiratory issues prompted surgical intervention. Multilevel thoracic PSO and thoracolumbar fusion were performed, resulting in improved lower-extremity function and correction of the kyphotic deformity to approximately 65°. This report outlines an unusual AT/RT presentation and postoperative course and also discusses literature related to PSO within the context of pediatric kyphotic deformity. The authors' experience supports the use of multilevel PSO with fusion as a potential treatment option for significant pediatric thoracolumbar kyphotic deformity requiring surgical correction.

Comparative effectiveness of ventral vs dorsal surgery for cervical spondylotic myelopathy.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction. OBJECTIVE: To determine the feasibility of a randomized clinical trial comparing the clinical effectiveness and costs of ventral vs dorsal decompression with fusion surgery for treating CSM. METHODS: A nonrandomized, prospective, clinical pilot trial was conducted. Patients ages 40 to 85 years with degenerative CSM were enrolled at 7 sites over 2 years (2007-2009). Outcome assessments were obtained preoperatively and at 3 months, 6 months, and 1 year postoperatively. A hospital-based economic analysis used costs derived from hospital charges and Medicare cost-to-charge ratios. RESULTS: The pilot study enrolled 50 patients. Twenty-eight were treated with ventral fusion surgery and 22 with dorsal fusion surgery. The average age was 61.6 years. Baseline demographics and health-related quality of life (HR-QOL) scores were comparable between groups; however, dorsal surgery patients had significantly more severe myelopathy (P<.01). Comprehensive 1-year follow-up was obtained in 46 of 50 patients (92%). Greater HR-QOL improvement (Short-Form 36 Physical Component Summary) was observed after ventral surgery (P=.05). The complication rate (16.6% overall) was comparable between groups. Significant improvement in the modified Japanese Orthopedic Association scale score was observed in both groups (P<.01). Dorsal fusion surgery had significantly greater mean hospital costs ($29 465 vs $19 245; P<.01) and longer average length of hospital stay (4.0 vs 2.6 days; P<.01) compared with ventral fusion surgery. CONCLUSION: Surgery for treating CSM was followed by significant improvement in disease-specific symptoms and in HR-QOL. Greater improvement in HR-QOL was observed after ventral surgery. Dorsal fusion surgery was associated with longer length of hospital stay and higher hospital costs. The pilot study demonstrated feasibility for a larger randomized clinical trial.

Cervical spine reoperation rates and hospital resource utilization after initial surgery for degenerative cervical spine disease in 12,338 patients in Washington State.

OBJECTIVE: Patients undergoing surgery for degenerative cervical spine disease may require future surgery for disease progression. We investigated factors related to the rate of additional cervical spine surgery, the associated length of stay, and hospital charges. METHODS: The was a longitudinal retrospective cohort study using Washington state's 1998 to 2002 state inpatient databases and International Classification of Diseases-Ninth Revision-Clinical Modification (ICD-9) codes to analyze patients undergoing degenerative cervical spine surgery. Multivariate Poisson regression to identify patient and surgical factors associated with reoperation for degenerative cervical spine disease was used. Multivariate linear regressions to identify factors associated with length of stay and hospital charges adjusted for age, sex, year of surgery, primary diagnosis, payment type, discharge status, and comorbidities were also used. RESULTS: A total of 12,338 patients underwent initial cervical spine surgeries from 1998 to 2002; the mean follow-up duration was 2.3 years, and 688 patients (5.6%) underwent a reoperation (2.5% per year). Higher reoperation rates were independently associated with younger patients (P < 0.001) and a primary diagnosis of disc herniation with myelopathy (P = 0.011). Ventral surgery (P < 0.001) and fusion (P < 0.001) were both associated with lower rates of reoperation; however, a high correlation (Spearman's rho = 0.82; P < 0.001) made it impossible to determine which factor was dominant. Longer length of stay was independently associated with nonventral approaches (+1.0 day; P < 0.001) and fusion surgery (+0.8 day; P < 0.001). Greater hospital charges were independently associated with nonventral approaches (+$2900; P < 0.001) and fusion surgery (+$9600; P < 0.001). CONCLUSION: Patients undergoing surgery for degenerative cervical spine disease undergo reoperations at the rate of 2.5% per year. An initial ventral approach and/or fusion seem to be associated with lower reoperation rates. An initial nonventral approach and fusion were more expensive.

Cervical radiculopathy: pathophysiology, presentation, and clinical evaluation.

Cervical radiculopathy is a common condition that usually results from compression and inflammation of the cervical nerve root or roots in the region of the neural foramen. It is frequently caused by cervical disc herniation and cervical spondylosis. The diagnosis can be established by history and physical examination, but care should be taken, as diagnoses can mimic or coexist with cervical radiculopathy, such as entrapment neuropathies. The pathophysiology, presentation, and clinical evaluation of cervical radiculopathy are discussed.

A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting.

ONYX-015 is an oncolytic virus untested as a treatment for malignant glioma. The NABTT CNS Consortium conducted a dose-escalation trial of intracerebral injections of ONYX-015. Cohorts of six patients at each dose level received doses of vector from 10(7) plaque-forming units (pfu) to 10(10) pfu into a total of 10 sites within the resected glioma cavity. Adverse events were identified on physical exams and testing of hematologic, renal, and liver functions. Efficacy data were obtained from serial MRI scans. None of the 24 patients experienced serious adverse events related to ONYX-015. The maximum tolerated dose was not reached at 10(10) pfu. The median time to progression after treatment with ONYX-015 was 46 days (range 13 to 452 + days). The median survival time was 6.2 months (range 1.3 to 28.0 + months). One patient has not progressed and 1 patient showed regression of interval-increased enhancement. With more than 19 months of follow-up, 1/6 recipients at a dose of 10(9) and 2/6 at a dose of 10(10) pfu remain alive. In 2 patients who underwent a second resection 3 months after ONYX-015 injection, a lymphocytic and plasmacytoid cell infiltrate was observed. Injection of ONYX-015 into glioma cavities is well tolerated at doses up to 10(10) pfu.